P1128: EVALUATION OF STANDARD OF CARE IN SECOND-LINE FOR PATIENTS WITH RELAPSED OR REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA IN THE PRE-CAR-T ERA: A DUTCH POPULATION-BASED STUDY
Authors: Elise R.A. Pennings, Müjde Durmaz, Otto Visser, Eduardus F.M. Posthuma, Djamila E. Issa, Martine E.D. Chamuleau, Anne M. Spanjaart, Tom van Meerten, Pim G.N.J. Mutsaers, Margot Jak, Suzanne van Dorp, Joost S.P. Vermaat, Marjolein W.M. van der Poel, Maria T. Kuipers, Frederick W. Thielen, Carin A. Uyl-de Groot, Pieternella J. Lugtenburg, Marie José Kersten, Avinash G. Dinmohamed
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Outcomes of patients with diffuse large B-cell lymphoma (DLBCL) who are refractory to or who relapse early after first-line therapy (i.e., “early R/R” DLBCL) are generally poor. Second-line treatment options for early R/R DLBCL include salvage immunochemotherapy followed by autologous stem cell transplantation (ASCT) for younger, fit patients and non-intensive regimens for older and unfit patients. In 2022, the European Medicines Agency approved the first CAR T-cell therapy (axicabtagene ciloleucel; axi-cel) to treat adults with early R/R DLBCL based on the results of the pivotal phase 3 ZUMA-7 trial. ZUMA-7 showed the efficacy of axi-cel for early R/R DLBCL patients eligible for second-line therapy with intensive, potentially curative therapy. With the emergence of novel second-line treatment options, evaluating the standard of care (SoC) for early R/R DLBCL in a real-world setting is necessary. However, these data are hitherto scarce. Aims: As a benchmark for novel treatments, we evaluated population-based outcomes of SoC in second-line for early R/R DLBCL patients in the Netherlands in the pre-CAR-T era. Methods: We selected adult patients (≥18 years) with DLBCL, transformed follicular lymphoma (tFL), and primary mediastinal B-cell lymphoma (PMBCL) diagnosed between 2014-2018 from the nationwide Netherlands Cancer Registry. Three inclusion criteria were used and based on ZUMA-7: 1) first-line treatment with an anti-CD20 monoclonal antibody and an anthracycline, 2) early R/R disease defined as either stable/progressive disease as best response to first-line treatment or partial/complete response and subsequent relapse ≤12 months from completion of first-line treatment, and (3) second-line treatment with an intensive regimen ±ASCT. Patients who received CAR T-cell therapy were excluded. Descriptive statistics were used to analyze baseline characteristics at the start of second-line treatment. Survival was assessed from start of second-line treatment until progression, start of subsequent treatment, death, or end of follow-up, whichever occurs first (event-free survival, EFS), or until death or end of follow-up (overall survival, OS), using the Kaplan-Meier method. Results: Of the 6,899 adult patients diagnosed with DLBCL, tFL, and PMBCL in the Netherlands between 2014-2018, 527 received second-line treatment for early R/R disease. After excluding patients who received non-intensive regimens (n=186) and CAR T-cell therapy recipients (n=33), 308 patients were included in our cohort (median age: 60 years; 7% ≥70 years; 66% males; 61% stage III-IV, 90% DLBCL, 6% tFL, 4% PMBCL). In 36% (n=111/308) of the included patients the intensive regimen was followed by ASCT. For 266 patients, the best response to second-line treatment was available, with overall response and complete remission rates of 51% (n=157) and 32% (n=98), respectively. With ≥3 years of follow-up, the median EFS was 3.3 months (95% confidence interval [CI], 2.7-4.2), with a 2-year EFS rate of 27% (95% CI: 22-32; Figure 1A). The median OS was 7.1 months (95% CI: 6.3-8.7), with a 2-year OS rate of 32% (95% CI: 27-38; Figure 1B). Summary/Conclusion: This population-based study demonstrated that in the real world pre-CAR-T era the survival of early R/R DLBCL patients treated with second-line intensive therapy ±ASCT is poor, highlighting the need for novel treatments to improve outcomes. Real-world data on SoC and population estimates facilitate comparison of (cost-)effectiveness and budget impact of novel treatments with usual care in clinical practice and help to shape the future treatment landscape for early R/R DLBCL.Keywords: Diffuse large B cell lymphoma, Real world data, relapsed/refractory, Outcome